Experimental analysis of mixed tuberculous and staphylococcal infection in albino mice

Summary In infection of mice with small doses ofM. tuberculosis the concomitant staphylococcal infection, especially that developing in advance, leads to attenuation of the tuberculous process.(Presented by Active Member of the Academy of Medical Sciences of the USSR Z. V. Ermol'eva) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 61, No. 5, pp. 90–91, May, 1966     

Analysis of enhancing effect of sand fly saliva on Leishmania infection in mice.

Salivary gland lysates of the sand fly Lutzomyia longipalpis markedly enhance the course of infection with Leishmania major in mice. Here we examine various parameters of this phenomenon. The exacerbative effect of L. longipalpis salivary gland lysates occurred in five different mouse strains; however, the character of the effect varied from one strain to another. Consistent exacerbation of infection was achieved with as little as 1/10 of a gland. The exacerbative effect applied to more than one Leishmania species and to more than one species of sand fly, since salivary gland lysates of L. longipalpis enhanced infection with L. mexicana amazonensis and salivary gland lysates of Phlebotomus papatasi enhanced infection with L. major. A synthetic rat calcitonin gene-related peptide was also found to exacerbate infection with L. major but was found to be approximately 100-fold less potent than saliva in mediating this effect. In addition, lesions induced at skin sites at which L. longipalpis had probed for a blood meal exhibited an exacerbated course of infection similar to that seen when parasites were injected with sand fly salivary gland lysates.     

Stimulation by staphylococcal enterotoxin A of nonspecific resistance of mice to microbial infection.

The effects of staphylococcal enterotoxins A, B, and C2 (SEA, SEB, and SEC2) on the resistance of mice to microbial infections were studied. SEA stimulated the resistance strongly, whereas SEB and SEC2 had no such effect. Treatment with SEA increased the number of peripheral blood polymorphonuclear leukocytes significantly within 4 h, and these polymorphonuclear leukocytes exhibited a higher chemiluminescence response than those of the controls. Furthermore, a significant increase in spleen weight was also observed in mice treated with SEA, and histologically that increase was characterized by a proliferation of lymphoblast-like cells which were stained with antibody to mouse Thy-1 but not with antibody to mouse immunoglobulin G by indirect immunofluorescence. As expected from the above findings, the treatment of nude mice (nu/nu) with SEA failed to protect them against Escherichia coli infections, whereas treatment of heterozygous (nu/+) controls afforded such protection. This was in part supported by the fact that the chemiluminescence response of peripheral blood polymorphonuclear leukocytes was increased significantly by treatment with SEA in nu/+mice but not in nu/nu mice.     

The role of suppressor cells in congenital influenza infection in mice

Young mice with congenital influenza infection have lower immune responsiveness of lymphocytes to nonspecific mitogens and influenza virus antigens. Lymphocytes of such animals inhibit proliferation of normal lymphoid cells activated with concanavalin A and immune lymphocytes activated with influenza virus antigens. It is assumed that in congenital influenza infection one of the possible mechanisms of immunosuppression in mice is the activation of suppressor T-cells.     

The role of staphylococcal superinfection in viral hepatitis

Viral hepatitis A was diagnosed in 69.35 percent of the 124 patients with viral hepatitides aged 15 to 62, 54.1 percent of these females and 45.9 percent males, and viral hepatitis B in 30.65 percent. The disease course varied in severity, was typical in all cases; the icteric form was observed in all the patients. An unfavorable pyoinflammatory premorbid background was present in 1/3 of the examinees. The studies have revealed that a staphylococcal superinfection with the icteric syndrome contributed to the pathogenesis of viral hepatitis. Antistaphylococcal agglutinins were detected in 65.6 percent of hepatitis A and in 73.7 percent of hepatitis B patients, and alpha antitoxins in 81.1 and 71.0 percent of patients, respectively. The disease severity correlated with high antitoxin titers, high antitoxin titers with a delayed convalescence of viral hepatitis A patients. Changes in the titers of antistaphylococcal agglutinins in hepatitis B patients were not rapid and their time course correlated with the terms of liver function recovery. The author comes to a conclusion that bacterial superinfection contributes to the pathogenesis of viral hepatitides, staphylococcal infection among other ones, that essentially influences the disease course.     

The role of interleukin-5 in protective immunity to Strongyloides venezuelensis infection in mice.

We depleted or neutralized interleukin-5 (IL-5) and IL-5 receptor of C57BL/6 mice, using rat anti-murine IL-5 monoclonal antibody (NC17) and anti-murine IL-5 receptor monoclonal antibody (H7). Mice treated with these monoclonal antibodies were infected with Strongyloides venezuelensis larvae. The time-course of faecal egg output and peripheral eosinophilia were monitored. In a primary infection, anti-IL-5 treatment did not affect faecal egg output, although the eosinophil count in peripheral blood was markedly reduced. There was no difference in intestinal worm burden or faecal egg output between anti-IL-5 treated and non-treated mice. In a secondary infection, worms were expelled from the small intestine of anti-IL-5-treated mice as well as from non-treated mice. Worm recovery from the lungs of mice treated with either anti-IL-5 or anti-IL-5 receptor monoclonal antibody was the same as that of normal controls. However, a marked reduction in worm recovery was observed in re-infected mice that had not been treated with monoclonal antibodies. Treatment with anti-IL-5 or anti-IL-5 receptor monoclonal antibody suppressed blood and tissue eosinophilia. Thus the results suggested that the host's protective immunity against tissue-migrating larvae was IL-5-dependent but intestinal immunity was not.     

Serum IL-2 inhibitor in mice. I. Increase during infection.

Serum from normal mice contains an inhibitor of interleukin-2 (IL-2) which probably interacts directly with IL-2. Athymic mice and normal mice kept under specific pathogen-free conditions do not show this activity, whereas mice infected with malaria parasites have increased serum levels of inhibitor. This IL-2 inhibitor may play an important part in regulating T-cell function.     

M-CSF transgenic mice: role of M-CSF in infection and autoimmunity.

In this study, transgenic CD2F1 mouse lines (C-1.1-C-1.11) bearing a transgene encoding the murine growth factor M-CSF under the control of the liver specific alpha-1-antitrypsin gene promoter were generated. Transgenic C-1.4 mice showed elevated expression of transgene-encoded M-CSF in the liver and displayed a 2-3-fold increase of M-CSF plasma levels and of macrophage numbers in the liver as compared with non-transgenic littermates. M-CSF transgenic mice showed increased resistance against sublethal i.v. infections with Listeria monocytogenes as compared with infected non-transgenic mice. To investigate the influence of M-CSF in murine systemic lupus erythematosus (SLE), the M-CSF transgenic mouse line C-1.4 was bred into the genetic background of SLE-prone MRL+/+ mice. The resulting C-1.4/MRL transgenic mice bearing increased endogenous M-CSF levels showed consistently lower levels of anti-ss-DNA autoantibodies as compared with non-transgenic MRL+/+ mice. The life span of the C- 1.4/MRL transgenic mice and the severity of the disease in these mice remained unchanged as compared with their non-transgenic littermates. It is concluded that in addition to M-CSF further factors must be involved in the acceleration of the autoimmune disease in SLE prone MRL/lpr mice.     

Cell-mediated immune phenomena induced by lymphokines from splenic lymphocytes of mice with chronic staphylococcal infection.

Splenic lymphocytes from normal mice and from mice displaying delayed hypersensitivity to Staphylococcus aureus were cultured in the presence or absence of specific staphylococcal antigens. The cell-free supernatant fluids from these lymphocyte cultures were assessed for their ability to alter the functional capacities of normal macrophages. It was found that supernatants from staphylococcus-immune cells cultured in vitro with antigen possessed migration inhibitory factor activity and also were capable of stimulating the incorporation of [14C]glucosamine into macrophage membrane glycoproteins. In addition, the lymphokine-containing supernatants were capable of inducing activation of normal macrophages so that they inhibited the multiplication of intracellular Listeria monocytogenes. Although it was not possible to snow any significant enhancement of intracellular killing of S. aureus by the activated macrophages, evidence is presented that suggests that cell-mediated immune responses to S. aureus may significantly enhance pahgocytosis of staphylococci and, thereby, may provide for their rapid clearance from extracellular fluids.     

The role of staphylococcal polysaccharide microcapsule expression in septicemia and septic arthritis.

Staphylococcus aureus arthritis is a rapidly progressive and highly erosive disease of the joints in which both host and bacterial factors are of pathogenic importance. One potential bacterial virulence factor is the ability to express a polysaccharide capsule (CP). Among 11 reported capsular serotypes, CP type 5 (CP5) and CP8 comprise 80 to 85% of all clinical blood isolates. The aim of this study was to assess the role of CP5 as a virulence factor in staphylococcal septicemia and septic arthritis with a recently established murine model of hematogenously spread S. aureus arthritis. NMRI mice were inoculated intravenously with S. aureus strains isogenic for expression of CP5, and clinical, bacteriological, serological, and histopathological progression of disease was studied. Inoculation of 7 x 10(6) CFU of S. aureus per mouse induced 55% mortality in the group inoculated with the CP-expressing bacteria, compared to 18% in the group inoculated with CP- mutants. A lower dose of inoculum (3 x 10[6] per mouse) did not give rise to mortality in mice inoculated with CP mutant strains, whereas 18% of the mice inoculated with the CP5-expressing S. aureus died. Importantly, mice inoculated with S. aureus expressing CP5 had a significantly higher frequency of arthritis and a more severe form of the disease. In vitro assays suggested that macrophages were not able to phagocytize CP5+ staphylococci as efficiently as they were CP5- strains. In addition, once phagocytized, CP5+ bacteria were less efficiently killed than CP- mutants. In summary, CP5 leads to a higher frequency of arthritis and a more severe course of the disease. This seems to be related to the effects of the downregulatory properties of CP on the ingestion and intracellular killing capacity of phagocytes. Our results clearly indicate that the expression of CP5 is a determinant of the virulence of S. aureus in arthritis and septicemia.